Analysis of the RPE transcriptome reveals dynamic changes during the development of the outer blood-retinal barrier.

The retinal pigment epithelium plays a central role in the physiology of the retina [1]. As the outer-blood retinal barrier, it regulates transport between the neural retina and fenestrated capillaries of the choroid. Among its functions, retinal pigment epithelium (RPE) regulates the ionic environment of the subretinal space, phagocytizes shed outer segments of photoreceptors and participates in the visual cycle by converting trans-retinal to the photosensitive cis isoform. Diseases of the RPE result in retinal degeneration and degeneration of the choriocapillaris [2-4]. Transplantation of RPE into diseased eyes has met with limited success, perhaps because the diseased environment was unable to provide the environmental signals that regulate normal RPE function. To explore that possibility, our lab has studied how tissue-tissue interactions are established during normal development to regulate RPE’s function as the outer blood-retinal barrier. The barrier consists of two components: Transcellular mechanisms regulate transport through the cells of the monolayer and establish transepithelial gradients. By contrast, tight junctions regulate diffusion through the paracellular spaces, which prevents transepithelial gradients from dissipating. Aside from an increase in melanin and minor changes in morphology, the differentiation of RPE was thought to be completed early in retinal development. More recent studies demonstrate changes in cell polarity, cellular metabolism and the expression of intercellular junctional proteins [5-13]. These tight and adherens junctions bind the monolayer together and regulate transepithelial diffusion through the paracellular spaces. Development of the RPE can be divided into three stages that relate to the development of the inner and outer segments of photoreceptors. Across vertebrate species, these developmental milestones of the neural retina appear to be linked to developmental milestones of the choroid, Bruch’s membrane and RPE [14,15]. Previous studies related the formation of tight junctions to these milestones [16]. In the early phase, before inner segments penetrate the outer limiting membrane, a rudimentary adherens junction binds the RPE monolayer together, but tight junctions are absent. Near the end of this phase, isolated tight junctional strands begin to appear. In the intermediate phase, which ends when outer segments begin to form, these strands gradually coalesce into a discontinuous network that encircles the cell. By mid-intermediate phase, the network becomes continuous and functional, but it ©2007 Molecular Vision